Pipeline Insight: Endometriosis - New therapies near market while more innovative targets still needed

Introduction

Endometriosis is a common yet poorly understood gynecological disease that affects women of reproductive age. Symptoms include severe chronic pelvic pain and infertility. Endometriosis affects over 17 million women across the seven major markets. Nonetheless, its complex symptomatology contributes to difficult diagnosis and unclear etiology obstructs the discovery of disease modifying approaches.

Scope

*Analysis of endometriosis etiology, symptomology, diagnosis, treatment, prevalence trends, and key unmet market needs.

*Review of the pre-clinical and clinical pipeline for new endometriosis therapies, including analysis of key R&D company strategies.

*In depth analysis of historic (200408) seven major markets and rest of the world trends with future (20092018) seven major market dynamics.

*Commercial and clinical assessment of key late-stage pipeline drugs, with opinion leader comment and region-specific sales forecasts to 2018.

Highlights

Environmental factors, increased awareness and diagnosis will cause the incidence of endometriosis to increase in the seven major markets. Drugs in the market are not curative and do not provide long term pain relief yet there are only 13 agents in clinical development for the potential treatment of endometriosis.

Although contraceptives and progestogens are commonly used to treat endometriosis, these are mainly used off label. Bayer Schering will be able to use its sales and marketing resource to overcome the challenging task of convincing physicians to use its new endometriosis specific drug Visanne (dienogest) over other hormonal contraceptives.

Neurocrine's elagolix is the first oral non peptide gonadotropin releasing hormone (GnRH) antagonist. Phase II trials have shown that it is effective in treating endometriosis and does not reduce bone mineral density during 6 months therapy. This will allow the drug to become market leading in 2018.

Reasons to Purchase

*Analyze competitive environment at time of product launch.

*Validate internal forecasts and market potential for pipeline products.

*Identify licensing opportunities based on company portfolio and market needs.


Report Highlights

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Overview 1
Catalyst 1
Summary 1
ABOUT DATAMONITOR HEALTHCARE 2
About the Genitourinary pharmaceutical analysis team 2
Executive Summary 3
Strategic scoping and focus 3
Datamonitor insight into the endometriosis market 3
Datamonitor pipeline assessment summary 5
Related reports 5
Table of Contents 6
1. Pipeline Overview and Dynamics 7
Key findings 7
Pipeline overview 8
Endometriosis research goals 8
Late-stage clinical endometriosis pipeline 8
Datamonitor pipeline assessment summary 12
Key companies involved in the endometriosis pipeline 13
Bayer Schering - women's health market leader 13
Hormonal contraceptives drive Bayer Schering's growth 13
Targeting endometriosis provides Bayer Schering with a unique opportunity 14
Bayer Schering can focus on a successful product differentiation strategy to further establish itself in the endometriosis market 15
Key R&D company strategies 16
2. Endometriosis - Market Potential 17
Key findings 17
Definition 18
Dynamic progression of endometriosis 19
Recurrence in endometriosis 20
Etiology 20
Retrograde menstruation 20
Genetic predisposition 22
Coelomic metaplasia 22
Lymphatic or vascular distribution 22
Immune system dysfunctions 22
Environmental influences 23
Symptoms 23
Risk factors 25
Diagnosis 26
Delay in diagnosis 27
Misdiagnosis 27
Differential diagnosis 28
Patient segmentation 28
Epidemiology 30
Seven major markets 30
There are over 17 million women with endometriosis across the seven major markets 30
Endometriosis is a common cause of chronic pelvic pain 32
6.3 million infertile women are also suffering from endometriosis across the seven major markets 33
Rest of the world 35
Canada and Australia - over 1.3 million women suffer from endometriosis 35
BRIC nations - endometriosis population set to grow to 159 million by 2018 36
Current treatment options 37
Treatment of pelvic pain 40
Nonsteroidal anti-inflammatory drugs 40
Hormonal contraceptives 40
Androgenic agents 41
Progestogens 42
Antiprogestogens 43
Gonadotropin releasing hormone analogs 43
Chinese medicine 44
Surgery 45
Treatment guidelines 45
Current gold standard 47
Lupron (leuprolide acetate, Abbott) 47
Efficacy similar to danazol 48
Side effects generally restrict use to 6 months 48
Sales for Lupron continue to decline 50
Current and future seven major market overview 51
Endometriosis market definition 51
Limitations in sizing the endometriosis market with IMS data 52
Seven major markets dynamics - endometriosis market will grow up to 2018 52
Regional dynamics - the US remains the largest market but Japan is the fastest growing. 54
Class dynamics - oral monophase contraceptives will remain market leaders for endometriosis treatment in 2018 57
Brand dynamics - key brands to lose leading status following generic incursion 59
Rest of the world snapshot 61
The global endometriosis market displays weak growth 61
The rest of the world accounted for 24.3% of the global market in 2008 62
The rest of the world outstrips the seven major markets in terms of volume 63
Canada shows strong growth between 2007 and 2008 but BRIC grows more between 2004 and 2008 65
Unmet need in endometriosis 67
Need for a non invasive diagnostic tool 68
Biomarkers could help diagnose and monitor treatment efficacy 69
Symptom-based questionnaire could be used in primary care setting to increase diagnosis rates and reduce misdiagnosis 70
Endometrial biopsy seems promising 70
Need to raise awareness both in the population and among physicians 71
Physician's need to be educated about the condition 72
Recruit celebrities as spokeswomen for the disease 72
Patient advocacy group and endometriosis societies 73
Use of the internet and social networking sites to raise awareness among young girls 74
Need for better drugs 74
Limited treatment options 74
Current treatments are not without side effects 75
Contraceptives and GnRH only result in a moderate symptomatic improvement 76
Treatment efficacy is not optimal in the long-term 76
Surgery is invasive and not the preferred treatment for patients 77
Treatments are not curative but only manage the pain and infertility 77
Need for nonhormonal drugs as alternative treatments 78
Need for increased funding in the disease 78
Target product profile versus current level of attainment 79
3. R&D Approach 81
Key findings 81
Clinical trial design in endometriosis 82
Patient inclusion 82
Clinical trial size 82
Placebo versus active control 83
Trial endpoints in endometriosis 84
Pain 85
Quality of Life 87
Disease regression and Infertility 88
4. Pipeline Analysis & Forecasts 89
Key findings 89
Overview 90
Pipeline summary 90
Comparative forecasts 91
Visanne (dienogest; Bayer Schering) 92
Drug overview 92
Drug profile 93
SWOT analysis 94
Clinical trial data 94
Datamonitor drug assessment for Visanne 97
Clinical attractiveness 98
Commercial attractiveness 100
Forecasts to 2018 101
Elagolix (NBI-56418; Neurocrine) 102
Drug overview 102
Drug profile 103
SWOT analysis 103
Clinical trial data 104
Ongoing clinical trials 108
Datamonitor drug assessment for elagolix 108
Clinical attractiveness 110
Commercial attractiveness 113
Forecasts to 2018 115
Other drugs in development for the treatment of endometriosis 117
Tanezumab (PF-04383119; Pfizer) 117
The non-hormonal treatment in the clinical pipeline , 117
Femathina (MPI-674; Meditrina) 118
Aromatase inhibitors could be used for endometriosis treatment 118
Cetrorelix (AEterna Zentaris) 119
Cetrorelix development for endometriosis treatment remains uncertain 119
Late-stage development compounds recently discontinued 120
Antiprogestogen development should be further investigated 121
5. Innovative Early-Stage Approaches 122
Key findings 122
Innovative stage pipeline for endometriosis 123
Blocking angiogenesis 123
Leptin receptor antagonist (Cancer Research Technology) 124
Anti-inflammatory drugs 125
DXL-1215 (InNexus Biotechnology) 125
17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) 125
HSD inhibitor (QuatRx Pharmaceuticals) 125
The future of treatment in endometriosis 126
Genetic profiling will increase prevention of endometriosis 126
Increased incidence will drive an improvement in research leading to improved treatments 126
Bibliography 128
Journal papers 128
Websites 136
Datamonitor reports 139
Conferences attended 139
APPENDIX 140
Methodology 140
Market sizing methodology 140
Sales calculations 140
Rest of the world sales calculations 141
Datamonitor forecast methodology 141
Product forecasts 141
Definition of a standard unit 141
Datamonitor drug assessment scorecard 141
Contributing experts 142
About Datamonitor 144
About Datamonitor Healthcare 144
About the Disease analysis team 144
Datamonitor consulting 145
Disclaimer 147
List of Tables
Table 1: R&D drug pipeline for endometriosis, 2009 9
Table 2: Endometriosis risk factors 25
Table 3: Diagnostic experience with endometriosis according to the type of physician seen first 27
Table 4: Endometriosis differential diagnosis 28
Table 5: Prevalence of endometriosis across the seven major markets, 2009 30
Table 6: Trends in the prevalence of endometriosis across the seven major markets (000s), 2009-2018 31
Table 7: Prevalence of endometriosis in women affected by chronic pelvic pain across the seven major markets, 2009 32
Table 8: Trends in the prevalence of endometriosis in women affected by chronic pelvic pain across the seven major markets (000s), 2009-2018 33
Table 9: Prevalence of endometriosis in infertile women across the seven major markets, 2009 34
Table 10: Trends in the prevalence of endometriosis in infertile women across the seven major markets (000s), 2009-2018 35
Table 11: Prevalence of endometriosis in Australia and Canada, 2009 35
Table 12: Trends in the prevalence of endometriosis in Australia and Canada (000s), 2009-2018 36
Table 13: Prevalence of endometriosis in the BRIC countries, 2009 36
Table 14: Trends in the prevalence of endometriosis in the BRIC countries (000s), 2009-2018 37
Table 15: Drugs approved for the treatment of endometriosis in the seven major markets, 2009 39
Table 16: Lupron (leuprolide acetate - drug profile, 2009 48
Table 17: Lupron (leuprolide acetate, Abbott) side-effect profile in endometriosis patients 49
Table 18: Lupron (leuprolide acetate, Abbott) effect on bone mineral density in patients with endometriosis 50
Table 19: ICD-10 codes used to define the endometriosis market 52
Table 20: Seven major market sales ($m) dynamics of the endometriosis market, 2004-2018 56
Table 21: Seven major market sales ($m) for endometriosis by ATC class, 2004-2018 59
Table 22: Seven major market sales ($m) for key brands in endometriosis treatment, 2004-2018 60
Table 23: Global sales ($m) dynamics of the endometriosis market, 2004-08 62
Table 24: Global endometriosis market sales ($m) split by region, 2004-08 65
Table 25: Key biomarkers investigated for the diagnosis of endometriosis, 2009 69
Table 26: Endometriosis support groups across the seven major markets, 2009 73
Table 27: Summary of pharmacotherapy side effects in endometriosis 75
Table 28: Ability of Lupron (leuprolide, Abbott) to meet unmet needs in endometriosis in the seven major markets, 2009 80
Table 29: Endpoints for endometriosis trials 85
Table 30: Summary of the Initiative on Methods, Measurements and Pain Assessments in Clinical Trials (IMMPACT) recommendations 86
Table 31: Endometriosis severity profile scoring system based upon the Biberoglu and Behrman Scale (1981) 87
Table 32: Summary of studies showing endometriosis effect on quality of life, 2009 88
Table 33: Key products in late-stage R&D pipeline for endometriosis, 2009 90
Table 34: Sales forecasts for key drugs in late-stage development for endometriosis in the seven major markets, 2009-2018 ($m) 91
Table 35: Forecast assumptions for key products in late-stage development for endometriosis across the seven major markets, 2009-2018 92
Table 36: Visanne (dienogest) - drug profile, 2009 93
Table 37: Summary of key clinical trials for Visanne (dienogest) 95
Table 38: Datamonitor drug assessment summary of Visanne (dienogest, Bayer Schering) for endometriosis, 2009 98
Table 39: Receptor selectivity of various progestins 99
Table 40: Sales forecasts for Visanne in endometriosis in the seven major markets, 2009-2018 ($m) 102
Table 41: Impacting factors on the revenues of Visanne in endometriosis, 2009-2018 102
Table 42: Elagolix - drug profile, 2009 103
Table 43: Elagolix: summary of key clinical trials 105
Table 44: Elagolix: Petal-702 study primary endpoint - preliminary results 106
Table 45: Elagolix: Petal-603 study primary endpoint - final results 107
Table 46: Elagolix: Phase II Tulip Petal study - key facts 108
Table 47: Datamonitor drug assessment summary of elagolix (Neurocrine) for endometriosis, 2009 110
Table 48: Elagolix: bone safety determined in the Petal-603 clinical trial 112
Table 49: Sales forecasts for elagolix in endometriosis in the seven major markets, 2009-2018 ($m) 116
Table 50: Impacting factors on the revenues of elagolix in endometriosis, 2009-2018 117
Table 51: Recently discontinued projects in endometriosis 120
Table 52: Preclinical pipeline for the treatment of endometriosis, 2009 123
Table 53: Rest of the world diagnostic value application 141
Table 54: Datamonitor drug assessment scorecard for late stage endometriosis drugs, 2009 142
List of Figures
Figure 1: Datamonitor endometriosis pipeline assessment summary, 2009 5
Figure 2: Endometriosis clinical pipeline by development stage, 2009 10
Figure 3: Endometriosis clinical pipeline by target, 2009 11
Figure 4: Endometriosis clinical pipeline by mode of administration, 2009 12
Figure 5: Datamonitor endometriosis pipeline assessment summary, 2009 13
Figure 6: Bayer Schering genitourinary therapy area sales performance ($m), 2004-08 14
Figure 7: Common endometrial lesion sites 19
Figure 8: Anatomy of retrograde menstruation 21
Figure 9: Endometriosis breakdown of symptoms 24
Figure 10: American Academy Family Physicians (AAFP) endometriosis treatment guidelines 46
Figure 11: European Society of Human Reproduction and Embryology (ESHRE) endometriosis treatment guidelines 47
Figure 12: Sales performance of Lupron (leuprolide, TAP Pharmaceutical) in endometriosis across the seven major markets, 2004-2018 51
Figure 13: Endometriosis market sales ($m) across the seven major markets, 2004-2018 53
Figure 14: Endometriosis market volume sales (IMS standard units sold) across the seven major markets, 2004-2018 54
Figure 15: Regional endometriosis market value sales ($m) in the across the seven major markets, 2004-08 55
Figure 16: Regional endometriosis market value sales ($m) in the across the seven major markets, 2008-2018 56
Figure 17: Seven major markets endometriosis-specific sales ($m) by ATC class, 2004-2018 58
Figure 18: Seven major market sales ($m) for key brands in endometriosis treatment, 2004-2018 60
Figure 19: Global endometriosis market sales value by region, 2004-08 62
Figure 20: Global hormonal endometriosis sales ($m) dynamics, 2004-08 63
Figure 21: Global endometriosis market volume (IMS standard units sold) and value ($) sales by region, 2008 64
Figure 22: Rest of the World endometriosis market sales value ($m), 2004-08 66
Figure 23: Rest of the world endometriosis regional market dynamics ($m), 2004-08 67
Figure 24: Unmet needs in endometriosis, 2009 68
Figure 25: Datamonitor endometriosis pipeline assessment summary, 2009 91
Figure 26: Visanne (dienogest; Bayer Schering) SWOT analysis, 2009 94
Figure 27: Datamonitor drug assessment summary of Visanne (dienogest, Bayer Schering) for endometriosis, 2009 97
Figure 28: Sales forecasts for Visanne (dienogest, Bayer Schering) in endometriosis in the seven major markets, 2009-2018 ($m) 101
Figure 29: Elagolix (Neurocrine) SWOT analysis, 2009 104
Figure 30: Datamonitor drug assessment summary of elagolix (Neurocrine) for endometriosis, 2009 109
Figure 31: Sales forecasts for elagolix (Neurocrine) in endometriosis in the seven major markets ($m), 2014-18 116

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List of Tables
Table 1: R&D drug pipeline for endometriosis, 2009 9
Table 2: Endometriosis risk factors 25
Table 3: Diagnostic experience with endometriosis according to the type of physician seen first 27
Table 4: Endometriosis differential diagnosis 28
Table 5: Prevalence of endometriosis across the seven major markets, 2009 30
Table 6: Trends in the prevalence of endometriosis across the seven major markets (000s), 2009-2018 31
Table 7: Prevalence of endometriosis in women affected by chronic pelvic pain across the seven major markets, 2009 32
Table 8: Trends in the prevalence of endometriosis in women affected by chronic pelvic pain across the seven major markets (000s), 2009-2018 33
Table 9: Prevalence of endometriosis in infertile women across the seven major markets, 2009 34
Table 10: Trends in the prevalence of endometriosis in infertile women across the seven major markets (000s), 2009-2018 35
Table 11: Prevalence of endometriosis in Australia and Canada, 2009 35
Table 12: Trends in the prevalence of endometriosis in Australia and Canada (000s), 2009-2018 36
Table 13: Prevalence of endometriosis in the BRIC countries, 2009 36
Table 14: Trends in the prevalence of endometriosis in the BRIC countries (000s), 2009-2018 37
Table 15: Drugs approved for the treatment of endometriosis in the seven major markets, 2009 39
Table 16: Lupron (leuprolide acetate - drug profile, 2009 48
Table 17: Lupron (leuprolide acetate, Abbott) side-effect profile in endometriosis patients 49
Table 18: Lupron (leuprolide acetate, Abbott) effect on bone mineral density in patients with endometriosis 50
Table 19: ICD-10 codes used to define the endometriosis market 52
Table 20: Seven major market sales ($m) dynamics of the endometriosis market, 2004-2018 56
Table 21: Seven major market sales ($m) for endometriosis by ATC class, 2004-2018 59
Table 22: Seven major market sales ($m) for key brands in endometriosis treatment, 2004-2018 60
Table 23: Global sales ($m) dynamics of the endometriosis market, 2004-08 62
Table 24: Global endometriosis market sales ($m) split by region, 2004-08 65
Table 25: Key biomarkers investigated for the diagnosis of endometriosis, 2009 69
Table 26: Endometriosis support groups across the seven major markets, 2009 73
Table 27: Summary of pharmacotherapy side effects in endometriosis 75
Table 28: Ability of Lupron (leuprolide, Abbott) to meet unmet needs in endometriosis in the seven major markets, 2009 80
Table 29: Endpoints for endometriosis trials 85
Table 30: Summary of the Initiative on Methods, Measurements and Pain Assessments in Clinical Trials (IMMPACT) recommendations 86
Table 31: Endometriosis severity profile scoring system based upon the Biberoglu and Behrman Scale (1981) 87
Table 32: Summary of studies showing endometriosis effect on quality of life, 2009 88
Table 33: Key products in late-stage R&D pipeline for endometriosis, 2009 90
Table 34: Sales forecasts for key drugs in late-stage development for endometriosis in the seven major markets, 2009-2018 ($m) 91
Table 35: Forecast assumptions for key products in late-stage development for endometriosis across the seven major markets, 2009-2018 92
Table 36: Visanne (dienogest) - drug profile, 2009 93
Table 37: Summary of key clinical trials for Visanne (dienogest) 95
Table 38: Datamonitor drug assessment summary of Visanne (dienogest, Bayer Schering) for endometriosis, 2009 98
Table 39: Receptor selectivity of various progestins 99
Table 40: Sales forecasts for Visanne in endometriosis in the seven major markets, 2009-2018 ($m) 102
Table 41: Impacting factors on the revenues of Visanne in endometriosis, 2009-2018 102
Table 42: Elagolix - drug profile, 2009 103
Table 43: Elagolix: summary of key clinical trials 105
Table 44: Elagolix: Petal-702 study primary endpoint - preliminary results 106
Table 45: Elagolix: Petal-603 study primary endpoint - final results 107
Table 46: Elagolix: Phase II Tulip Petal study - key facts 108
Table 47: Datamonitor drug assessment summary of elagolix (Neurocrine) for endometriosis, 2009 110
Table 48: Elagolix: bone safety determined in the Petal-603 clinical trial 112
Table 49: Sales forecasts for elagolix in endometriosis in the seven major markets, 2009-2018 ($m) 116
Table 50: Impacting factors on the revenues of elagolix in endometriosis, 2009-2018 117
Table 51: Recently discontinued projects in endometriosis 120
Table 52: Preclinical pipeline for the treatment of endometriosis, 2009 123
Table 53: Rest of the world diagnostic value application 141
Table 54: Datamonitor drug assessment scorecard for late stage endometriosis drugs, 2009 142

List of Figures
Figure 1: Datamonitor endometriosis pipeline assessment summary, 2009 5
Figure 2: Endometriosis clinical pipeline by development stage, 2009 10
Figure 3: Endometriosis clinical pipeline by target, 2009 11
Figure 4: Endometriosis clinical pipeline by mode of administration, 2009 12
Figure 5: Datamonitor endometriosis pipeline assessment summary, 2009 13
Figure 6: Bayer Schering genitourinary therapy area sales performance ($m), 2004-08 14
Figure 7: Common endometrial lesion sites 19
Figure 8: Anatomy of retrograde menstruation 21
Figure 9: Endometriosis breakdown of symptoms 24
Figure 10: American Academy Family Physicians (AAFP) endometriosis treatment guidelines 46
Figure 11: European Society of Human Reproduction and Embryology (ESHRE) endometriosis treatment guidelines 47
Figure 12: Sales performance of Lupron (leuprolide, TAP Pharmaceutical) in endometriosis across the seven major markets, 2004-2018 51
Figure 13: Endometriosis market sales ($m) across the seven major markets, 2004-2018 53
Figure 14: Endometriosis market volume sales (IMS standard units sold) across the seven major markets, 2004-2018 54
Figure 15: Regional endometriosis market value sales ($m) in the across the seven major markets, 2004-08 55
Figure 16: Regional endometriosis market value sales ($m) in the across the seven major markets, 2008-2018 56
Figure 17: Seven major markets endometriosis-specific sales ($m) by ATC class, 2004-2018 58
Figure 18: Seven major market sales ($m) for key brands in endometriosis treatment, 2004-2018 60
Figure 19: Global endometriosis market sales value by region, 2004-08 62
Figure 20: Global hormonal endometriosis sales ($m) dynamics, 2004-08 63
Figure 21: Global endometriosis market volume (IMS standard units sold) and value ($) sales by region, 2008 64
Figure 22: Rest of the World endometriosis market sales value ($m), 2004-08 66
Figure 23: Rest of the world endometriosis regional market dynamics ($m), 2004-08 67
Figure 24: Unmet needs in endometriosis, 2009 68
Figure 25: Datamonitor endometriosis pipeline assessment summary, 2009 91
Figure 26: Visanne (dienogest; Bayer Schering) SWOT analysis, 2009 94
Figure 27: Datamonitor drug assessment summary of Visanne (dienogest, Bayer Schering) for endometriosis, 2009 97
Figure 28: Sales forecasts for Visanne (dienogest, Bayer Schering) in endometriosis in the seven major markets, 2009-2018 ($m) 101
Figure 29: Elagolix (Neurocrine) SWOT analysis, 2009 104
Figure 30: Datamonitor drug assessment summary of elagolix (Neurocrine) for endometriosis, 2009 109
Figure 31: Sales forecasts for elagolix (Neurocrine) in endometriosis in the seven major markets ($m), 2014-18 116
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